Impact of Ninjin'Yoeito on Fatigue in Patients Receiving Nab-Paclitaxel Plus Gemcitabine Therapy: A Prospective, Single-Arm, Phase II Open Label, Nonrandomized, Historically-Controlled Study

Abstract

Background: Ninjin'yoeito, a traditional Japanese herbal medicine, is used to prevent fatigue, loss of appetite, and coldness of limbs. Fatigue is an especially common issue during chemotherapy and can affect quality of life and the ability to complete scheduled treatment.

Objectives: This prospective exploratory trial evaluates the efficacy of ninjin'yoeito for fatigue in patients undergoing nab-paclitaxel plus gemcitabine therapy for unresectable pancreatic cancer. The primary end point was evaluation of fatigue according to Functional Assessment of Chronic Illness Therapy-Fatigue score during 2 courses of nab-paclitaxel plus gemcitabine therapy. Secondary end points included evaluation of dose intensity, appetite loss using numerical rating scale, and peripheral neuropathy using a patient neurotoxicity questionnaire.

Methods: We compared data from this interventional trial with a prior observational trial without administration of ninjin'yoeito with identical definition of end points (UMIN000021758). Thirty patients were required by the study.

Results: Threshold mean of Functional Assessment of Chronic Illness Therapy-Fatigue score across 8 weeks during chemotherapy was under 5.3 (P = 0.002). Secondary end points did not reveal any specific patterns in appetite loss or degree of pain. No significant changes in patient neurotoxicity questionnaire concerning sensory/motor disorders were observed, but the mean (SD) incidence of patients with sensory disturbance was higher between the fifth and eighth weeks (8.8 [1.26]) than during the first and fourth weeks (4.8 [0.96]) (P = 0.003). Clinically significant adverse reactions of ninjin'yoeito were not observed.

Conclusions: Ninjin'yoeito may be useful for improving the symptoms of fatigue caused by nab-paclitaxel plus gemcitabine in patients with unresectable pancreatic cancer. UMIN Clinical Trials Registry identifier: UMIN000025606. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Keywords: Fatigue; Japanese herbal medicine; Nab-paclitaxel plus gemcitabine; Ninjin'yoeito; Supportive therapy.

Figure 1

Consolidated Standards of Reporting Trials diagram.

Figure 2

Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score. FACIT-F was evaluated by the mean of the degrees; each degree was converted to numerical values as follows: 0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 4 = very much. The y-axis represents the total number of values. Total values were recorded weekly for each questionnaire. Threshold mean of FACIT-F score until 8 weeks during chemotherapy was under 5.3 (P = 0.002).

Figure 3

Change in numerical rating scale (NRS) score. Graphical data of appetite loss evaluated by NRS. There were no specific patterns.